Department of Ophthalmology, College of Medicine, King Saud University, King Abdulaziz University Hospital, Old Airport Road, PO Box 245, Riyadh 11411, Saudi Arabia.
Mediators Inflamm. 2013;2013:863036. doi: 10.1155/2013/863036. Epub 2013 May 20.
To test the hypothesis that brain-derived neurotrophic factor-(BDNF-) mediated neuroprotection is reduced by high-mobility group box-1 (HMGB1) in diabetic retina, paired vitreous and serum samples from 46 proliferative diabetic retinopathy and 34 nondiabetic patients were assayed for BDNF, HMGB1, soluble receptor for advanced glycation end products (sRAGE), soluble intercellular adhesion molecule-1 (sICAM-1), monocyte chemoattractant protein-1 (MCP-1), and TBARS. We also examined retinas of diabetic and HMGB1 intravitreally injected rats. The effect of the HMGB1 inhibitor glycyrrhizin on diabetes-induced changes in retinal BDNF expressions was studied. Western blot, ELISA, and TBARS assays were used. BDNF was not detected in vitreous samples. BDNF levels were significantly lower in serum samples from diabetic patients compared with nondiabetics, whereas HMGB1, sRAGE, sICAM-1, and TBARS levels were significantly higher in diabetic serum samples. MCP-1 levels did not differ significantly. There was significant inverse correlation between serum levels of BDNF and HMGB1. Diabetes and intravitreal administration of HMGB1 induced significant upregulation of the expression of HMGB1, TBARS, and cleaved caspase-3, whereas the expression of BDNF and synaptophysin was significantly downregulated in rat retinas. Glycyrrhizin significantly attenuated diabetes-induced downregulation of BDNF. Our results suggest that HMGB1-induced downregulation of BDNF might be involved in pathogenesis of diabetic retinal neurodegeneration.
为了验证高迁移率族蛋白 B1（HMGB1）是否会降低脑源性神经营养因子（BDNF）介导的糖尿病视网膜神经保护作用这一假说，我们检测了 46 例增殖性糖尿病视网膜病变患者和 34 例非糖尿病患者的配对玻璃体和血清样本中的 BDNF、HMGB1、晚期糖基化终产物可溶性受体（sRAGE）、可溶性细胞间黏附分子-1（sICAM-1）、单核细胞趋化蛋白-1（MCP-1）和 TBARS 的水平。我们还检查了糖尿病和 HMGB1 玻璃体注射大鼠的视网膜。研究了 HMGB1 抑制剂甘草甜素对糖尿病诱导的视网膜 BDNF 表达变化的影响。采用 Western blot、ELISA 和 TBARS 检测方法。玻璃体液中未检测到 BDNF。与非糖尿病患者相比，糖尿病患者血清样本中的 BDNF 水平明显降低，而 HMGB1、sRAGE、sICAM-1 和 TBARS 水平则明显升高。MCP-1 水平无明显差异。血清 BDNF 水平与 HMGB1 水平呈显著负相关。糖尿病和玻璃体注射 HMGB1 均诱导 HMGB1、TBARS 和裂解 caspase-3 的表达显著上调，而 BDNF 和突触小体蛋白的表达则显著下调。甘草甜素显著减轻了糖尿病诱导的 BDNF 下调。我们的研究结果表明，HMGB1 诱导的 BDNF 下调可能参与了糖尿病性视网膜神经退行性变的发病机制。
